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Molecular Mechanism(s) of Non-steroidal Anti-inflammatory Drugs in the Prevention of Metabolic Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 32290

Special Issue Editors

Dr. Seung Joon Baek

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Guest Editor
Laboratory of Signal Transduction, College of Veterinary Medicine, Seoul National University, Korea
Interests: NSAIDs; cancer chemoprevention; phytochemicals; TGF-beta superfamily; alternative splicing
Dr. Thomas Eling

E-Mail
Guest Editor
National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, USA
Interests: eicosanoid biochemistry; cyclooygenase; lipooxygenase; cancer prevention

Special Issue Information

Dear Colleagues,

The prevention of metablolic dieseases such as cancer, obesity, diabetes, and other inflammatory related diseases is an emerging research topic. Considerable research is currently directed toward the development of molecular target-based interventions, and a number of antitumorigenic and anti-inflammatory compounds have been developed and tested. Of these interventions, cyclooxygenase inhibitors have a particularly potent preventive and therapeutic value. Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs that target the activity of cyclooxygenase-1 or cyclooxygenase-2.

NSAIDs modulate not only cyclooxygenase activity but also many regulatory proteins including transcription factors, enzymes, cytokines, and growth factors. NSAIDs are known to be COX-dependent. However, in the last decade, considerable research has been published on the COX-independent pathway to support the hypothesis that NSAIDs may play an important role in other pathways.

This Special Issue is primarily focused on the prevention of metabolic diseases in regard to NSAIDs and their dependency and independency on cyclooxygenases. Future discoveries of NSAIDs and their potential targets in metabolic diseases could in turn establish new discoveries, helping us to understand the mechanisms of these diseases.

Dr. Seung Joon Baek
Dr. Thomas Eling
Guest Editors

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Keywords

  • NSAIDs
  • Metabolic diseases
  • chemoprevention
  • COX-dependent and -independent manner

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Published Papers (3 papers)

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Review

32 pages, 1504 KiB  
Review
NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase
by Oluwafunke R. Kolawole and Khosrow Kashfi
Int. J. Mol. Sci. 2022, 23(3), 1432; https://doi.org/10.3390/ijms23031432 - 27 Jan 2022
Cited by 79 | Viewed by 11087
Abstract
Acute inflammation or resolved inflammation is an adaptive host defense mechanism and is self-limiting, which returns the body to a state of homeostasis. However, unresolved, uncontrolled, or chronic inflammation may lead to various maladies, including cancer. Important evidence that links inflammation and cancer [...] Read more.
Acute inflammation or resolved inflammation is an adaptive host defense mechanism and is self-limiting, which returns the body to a state of homeostasis. However, unresolved, uncontrolled, or chronic inflammation may lead to various maladies, including cancer. Important evidence that links inflammation and cancer is that nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, reduce the risk and mortality from many cancers. The fact that NSAIDs inhibit the eicosanoid pathway prompted mechanistic drug developmental work focusing on cyclooxygenase (COX) and its products. The increased prostaglandin E2 levels and the overexpression of COX-2 in the colon and many other cancers provided the rationale for clinical trials with COX-2 inhibitors for cancer prevention or treatment. However, NSAIDs do not require the presence of COX-2 to prevent cancer. In this review, we highlight the effects of NSAIDs and selective COX-2 inhibitors (COXIBs) on targets beyond COX-2 that have shown to be important against many cancers. Finally, we hone in on specialized pro-resolving mediators (SPMs) that are biosynthesized locally and, in a time, -dependent manner to promote the resolution of inflammation and subsequent tissue healing. Different classes of SPMs are reviewed, highlighting aspirin’s potential in triggering the production of these resolution-promoting mediators (resolvins, lipoxins, protectins, and maresins), which show promise in inhibiting cancer growth and metastasis. Full article
(This article belongs to the Special Issue Molecular Mechanism(s) of Non-steroidal Anti-inflammatory Drugs in the Prevention of Metabolic Diseases)
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Graphical abstract

18 pages, 1084 KiB  
Review
Novel Applications of NSAIDs: Insight and Future Perspectives in Cardiovascular, Neurodegenerative, Diabetes and Cancer Disease Therapy
by Edmundas Kaduševičius
Int. J. Mol. Sci. 2021, 22(12), 6637; https://doi.org/10.3390/ijms22126637 - 21 Jun 2021
Cited by 35 | Viewed by 9313
Abstract
Once it became clear that inflammation takes place in the modulation of different degenerative disease including neurodegenerative, cardiovascular, diabetes and cancer the researchers has started intensive programs evaluating potential role of non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention or therapy of these diseases. [...] Read more.
Once it became clear that inflammation takes place in the modulation of different degenerative disease including neurodegenerative, cardiovascular, diabetes and cancer the researchers has started intensive programs evaluating potential role of non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention or therapy of these diseases. This review discusses the novel mechanism of action of NSAIDs and its potential use in the pharmacotherapy of neurodegenerative, cardiovascular, diabetes and cancer diseases. Many different molecular and cellular factors which are not yet fully understood play an important role in the pathogenesis of inflammation, axonal damage, demyelination, atherosclerosis, carcinogenesis thus further NSAID studies for a new potential indications based on precise pharmacotherapy model are warranted since NSAIDs are a heterogeneous group of medicines with relative different pharmacokinetics and pharmacodynamics profiles. Hopefully the new data from studies will fill in the gap between experimental and clinical results and translate our knowledge into successful disease therapy. Full article
(This article belongs to the Special Issue Molecular Mechanism(s) of Non-steroidal Anti-inflammatory Drugs in the Prevention of Metabolic Diseases)
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18 pages, 1342 KiB  
Review
Mechanisms of Colorectal Cancer Prevention by Aspirin—A Literature Review and Perspective on the Role of COX-Dependent and -Independent Pathways
by Ranjini Sankaranarayanan, D. Ramesh Kumar, Meric A. Altinoz and G. Jayarama Bhat
Int. J. Mol. Sci. 2020, 21(23), 9018; https://doi.org/10.3390/ijms21239018 - 27 Nov 2020
Cited by 51 | Viewed by 11092
Abstract
Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions [...] Read more.
Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions have been well studied and occur through inhibition of cyclooxygenases (COX). Interestingly, a vast amount of epidemiological, preclinical and clinical studies have revealed aspirin as a promising chemopreventive agent, particularly against colorectal cancers (CRC); however, the primary mechanism by which it decreases the occurrences of CRC has still not been established. Numerous mechanisms have been proposed for aspirin’s chemopreventive properties among which the inhibition of COX enzymes has been widely discussed. Despite the wide attention COX-inhibition has received as the most probable mechanism of cancer prevention by aspirin, it is clear that aspirin targets many other proteins and pathways, suggesting that these extra-COX targets may also be equally important in preventing CRC. In this review, we discuss the COX-dependent and -independent pathways described in literature for aspirin’s anti-cancer effects and highlight the strengths and limitations of the proposed mechanisms. Additionally, we emphasize the potential role of the metabolites of aspirin and salicylic acid (generated in the gut through microbial biotransformation) in contributing to aspirin’s chemopreventive actions. We suggest that the preferential chemopreventive effect of aspirin against CRC may be related to direct exposure of aspirin/salicylic acid or its metabolites to the colorectal tissues. Future investigations should shed light on the role of aspirin, its metabolites and the role of the gut microbiota in cancer prevention against CRC. Full article
(This article belongs to the Special Issue Molecular Mechanism(s) of Non-steroidal Anti-inflammatory Drugs in the Prevention of Metabolic Diseases)
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